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Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation

ABSTRACT: Autoimmune diseases such as multiple sclerosis (MS) develop because of failed peripheral immune tolerance for a specific self-antigen (Ag). Numerous approaches for Ag-specific suppression of autoimmune neuroinflammation have been proven in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. One such approach is intravenous (i.v.) tolerance induction by injecting a myelin Ag used for EAE induction. However, the translation of this and similar experimental strategies into therapy for MS has been hampered by uncertainty regarding relevant myelin Ags in MS patients. To address this issue, we developed a therapeutic strategy that relies on oligodendrocyte (Ol)-derived extracellular vesicles (Ol-EVs), which naturally contain multiple myelin Ags. Ol-EVs injected i.v. suppressed disease in a myelin Ag-dependent manner, both prophylactically and therapeutically, in several EAE models. The treatment was safe and restored immune tolerance by inducing immunosuppressive monocytes and apoptosis of autoreactive encephalitogenic CD4+ T cells. Finally, we show that human Ols also release EVs containing most relevant myelin Ags, providing a basis for their use in MS therapy. These findings introduce an approach for suppressing central nervous system autoimmunity in a myelin Ag-specific manner.

INSTRUMENT(S): Thermo Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Abdolmohamad Rostami

PROVIDER: MSV000085434 | MassIVE | Sun May 17 19:53:00 BST 2020

SECONDARY ACCESSION(S): PXD019246

REPOSITORIES: MassIVE

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